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The transcription factor CDX2 maintains active enhancer in intestinal villus cells in vivo

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE34568 | GEO | 2013/02/05

SECONDARY ACCESSION(S): PRJNA151027

REPOSITORIES: GEO

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The transcription factor CDX2 maintains active enhancer in intestinal villus cells in vivo

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-02-05 | E-GEOD-34568 | biostudies-arrayexpress

The transcription factor CDX2 maintains active enhancer in intestinal villus cells in vivo (expression data)

Project description:We established whether partner transcription factor binding, chromatin structure, or gene expression is compromised upon loss of partner factors cdx2 or hnf4a in mouse intestinal villi This metadata file describes the gene expression componant of that data Intestinal epithelia were collected from mouse jejunum using EDTA-based chelation and RNA was made using trizol. RNA was checked for quality and then processed for affymetrix arrays, 430 2.0.

2013-02-05 | E-GEOD-34567 | biostudies-arrayexpress

The transcription factor CDX2 maintains active enhancer in intestinal villus cells in vivo (expression data)

2013-02-05 | GSE34567 | GEO

The transcription factor CDX2 maintains active enhancer in intestinal villus cells in vivo (ChIP-seq data)

Project description:We established whether partner transcription factor binding, chromatin structure, or gene expression is compromised upon loss of partner factors cdx2 or hnf4a in mouse intestinal villi. This metadata file describes the ChIP-seq componant of that data Intestinal epithelia were collected from mouse jejunum using EDTA-based chelation and ChIP-seq was performed, followed by next generation sequencing.

2013-02-05 | E-GEOD-34566 | biostudies-arrayexpress

The transcription factor CDX2 maintains active enhancer in intestinal villus cells in vivo (ChIP-seq data)

2013-02-05 | GSE34566 | GEO

Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.

Project description:Tissue-specific gene expression requires modulation of nucleosomes, allowing transcription factors to occupy cis elements that are accessible only in selected tissues. Master transcription factors control cell-specific genes and define cellular identities, but it is unclear if they possess special abilities to regulate cell-specific chromatin and if such abilities might underlie lineage determination and maintenance. One prevailing view is that several transcription factors enable chromatin access in combination. The homeodomain protein CDX2 specifies the embryonic intestinal epithelium, through unknown mechanisms, and partners with transcription factors such as HNF4A in the adult intestine. We examined enhancer chromatin and gene expression following Cdx2 or Hnf4a excision in mouse intestines. HNF4A loss did not affect CDX2 binding or chromatin, whereas CDX2 depletion modified chromatin significantly at CDX2-bound enhancers, disrupted HNF4A occupancy, and abrogated expression of neighboring genes. Thus, CDX2 maintains transcription-permissive chromatin, illustrating a powerful and dominant effect on enhancer configuration in an adult tissue. Similar, hierarchical control of cell-specific chromatin states is probably a general property of master transcription factors.

| S-EPMC3554120 | biostudies-literature

Cdx2 transcription factor binding in intestinal villus and gene expression profiling in Cdx mutant mice

Project description:We conditionally inactivated mouse Cdx2, a dominant regulator of intestinal development, and mapped its genome occupancy in adult intestinal villi. Although homeotic transformation, observed in Cdx2-null embryos, was absent in mutant adults, gene expression and cell morphology were vitally compromised. Lethality was accelerated in mice lacking both Cdx2 and its homolog Cdx1, with exaggeration of defects in crypt cell replication and enterocyte differentiation. Cdx2 occupancy correlated with hundreds of transcripts that fell but not with equal numbers that rose with Cdx loss, indicating a predominantly activating role at intestinal cis-regulatory regions. Integrated consideration of a mutant phenotype and cistrome hence reveals the continued and distinct requirement in adults of a master developmental regulator that activates tissue-specific genes.

2011-04-13 | GSE24633 | GEO

Distinct Processes and Transcriptional Targets Underlie CDX2 Requirements in Intestinal Stem Cells and Differentiated Villus Cells.

Project description:Lgr5-expressing intestinal stem cells (ISCs) renew the adult gut epithelium by producing mature villus cells (VCs); the transcriptional basis for ISC functions remains unclear. RNA sequencing analysis identified transcripts modulated during differentiation of Lgr5(+) ISCs into VCs, with high expression of the intestine-restricted transcription factor (TF) gene Cdx2 in both populations. Cdx2-deleted mouse ISCs showed impaired proliferation and long-term inability to produce mature lineages, revealing essential ISC functions. Chromatin immunoprecipitation sequencing analysis of CDX2 in Lgr5(+) ISCs, coupled with mRNA profiling of control and Cdx2(-/-) ISCs, identified features of CDX2 regulation distinct from VCs. Most CDX2 binding in ISCs occurs in anticipation of future gene expression, but whereas CDX2 primarily activates VC genes, direct ISC targets are activated and repressed. Diverse CDX2 requirements in stem and differentiated cells may reflect the versatility of TFs that specify a tissue in development and control the same tissue in adults.

| S-EPMC4649135 | biostudies-literature

Cdx2 transcription factor binding in intestinal villus and gene expression profiling in Cdx mutant mice

2011-04-13 | E-GEOD-24633 | biostudies-arrayexpress

Transcription factors GATA4 and HNF4A control distinct aspects of intestinal homeostasis in conjunction with transcription factor CDX2.

Project description:Distinct groups of transcription factors (TFs) assemble at tissue-specific cis-regulatory sites, implying that different TF combinations may control different genes and cellular functions. Within such combinations, TFs that specify or maintain a lineage and are therefore considered master regulators may play a key role. Gene enhancers often attract these tissue-restricted TFs, as well as TFs that are expressed more broadly. However, the contributions of the individual TFs to combinatorial regulatory activity have not been examined critically in many cases in vivo. We address this question using a genetic approach in mice to inactivate the intestine-specifying and intestine-restricted factor CDX2 alone or in combination with its more broadly expressed partner factors, GATA4 and HNF4A. Compared with single mutants, each combination produced significantly greater defects and rapid lethality through distinct anomalies. Intestines lacking Gata4 and Cdx2 were deficient in crypt cell replication, whereas combined loss of Hnf4a and Cdx2 specifically impaired viability and maturation of villus enterocytes. Integrated analysis of TF binding and of transcripts affected in Hnf4a;Cdx2 compound-mutant intestines indicated that this TF pair controls genes required to construct the apical brush border and absorb nutrients, including dietary lipids. This study thus defines combinatorial TF activities, their specific requirements during tissue homeostasis, and modules of transcriptional targets in intestinal epithelial cells in vivo.

| S-EPMC4340426 | biostudies-literature

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